atterns of gastroenterologists and colorectal surgeons in the management of acute severe ulcerative colitis but was associated with similar outcomes to a historical cohort. Despite continued use of high-dose corticosteroids and biologicals, the incidence of COVID-19 within 3 months was low and not associated with adverse COVID-19 outcomes.
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None.Human pluripotent stem cells show considerable promise for applications in regenerative medicine, including the development of cell replacement paradigms for the treatment of Parkinson's disease. https://www.selleckchem.com/products/cq211.html Protocols have been developed to generate authentic midbrain dopamine (mDA) neurons capable of reversing dopamine-related deficits in animal models of Parkinson's disease. However, the generation of mDA neurons at clinical scale suitable for human application remains an important challenge. Here, we present an mDA neuron derivation protocol based on a two-step WNT signaling activation strategy that improves expression of midbrain markers, such as Engrailed-1 (EN1), while minimizing expression of contaminating posterior (hindbrain) and anterior (diencephalic) lineage markers. The resulting neurons exhibit molecular, biochemical, and electrophysiological properties of mDA neurons. Cryopreserved mDA neuron precursors can be successfully transplanted into 6-hydroxydopamine (6OHDA) lesioned rats to induce recovery of amphetamine-induced rotation behavior. The protocol presented here is the basis for clinical-grade mDA neuron production and preclinical safety and efficacy studies.Parkinson's disease is characterized by the loss of dopaminergic neurons in the substantia nigra leading to disabling deficits. Dopamine neuron grafts may provide a significant therapeutic advance over current therapies. We have generated midbrain dopamine neurons from human embryonic stem cells and manufactured large-scale cryopreserved dopamine progenitors for clinical use. After optimizing cell survival and phenotypes in short-term studies, the cell product, MSK-DA01, was subjected to an extensive set of biodistribution, toxicity, and tumorigenicity assessments in mice under GLP conditions. A large-scale efficacy study was also performed in rats with the same lot of cells intended for potential human use and demonstrated survival of the grafted cells and behavioral amelioration in 6-hydroxydopamine lesioned rats. There were no adverse effects attributable to the grafted cells, no obvious distribution outside the brain, and no cell overgrowth or tumor formation, thus paving the way for a future clinical trial.Sickle cell disease (SCD) is caused by a well-defined point mutation in the β-globin gene and therefore is an optimal target for hematopoietic stem cell (HSC) gene-addition/editing therapy. In HSC gene-addition therapy, a therapeutic β-globin gene is integrated into patient HSCs via lentiviral transduction, resulting in long-term phenotypic correction. State-of-the-art gene-editing technology has made it possible to repair the β-globin mutation in patient HSCs or target genetic loci associated with reactivation of endogenous γ-globin expression. With both approaches showing signs of therapeutic efficacy in patients, we discuss current genetic treatments, challenges, and technical advances in this field.Epigenetic memories play an important part in regulating stem cell identities. Tools from the theory of non-Markov processes may help us understand these memories better and develop a more integrated view of stem cell fate and function.COVID-19 has unfortunately halted lab work, conferences, and in-person networking, which is especially detrimental to researchers just starting their labs. Through social media and our reviewer networks, we met some early-career stem cell investigators impacted by the closures. Here, they introduce themselves and their research to our readers.Cell-based therapy is expected as an alternative treatment for Parkinson's disease. In this issue of Cell Stem Cell, two accompanying papers (Kim et al., 2021; Piao et al., 2021) report the induction of clinically applicable dopaminergic neurons from human embryonic stem cells and the results of pre-clinical study toward a clinical trial.Current in vitro systems are powerful tools for studying early heart specification but lack the ability to model morphological events. Reporting in this issue of Cell Stem Cell, Rossi et al. (2021) present a patterned embryonic organoid model (gastruloid) that mimics aspects of early cardiogenesis.Adult neural stem cells (NSCs) have the ability to oscillate between activated and dormant states in response to extrinsic regulators. In this issue of Cell Stem Cell, Belenguer et al. (2020) identify a direct role for systemic TNF-α, which acts through its receptors TNFRII and TNFRI as a regulator of NSC activation and a return to quiescence, respectively.In this issue of Cell Stem Cell, De Belly et al. (2021) and Bergert et al. (2021) reveal that membrane tension regulates the pluripotent state via endocytosis-mediated ERK signaling. These findings advance our understanding of naive pluripotency and highlight how cell mechanics are intertwined with molecular signaling to drive cell fate decisions.Tobacco use is a leading preventable cause of morbidity and mortality worldwide. Little is known about recent prevalence and trends in tobacco use among adolescents globally. We aimed to assess the recent global prevalence of tobacco use in young adolescents and the secular trends in prevalence between 1999 and 2018.
We used the most recent Global Youth Tobacco Surveys data on adolescents aged 13-15 years from 143 countries or territories that had done at least one survey between Jan 1, 2010, and Dec 31, 2018, to assess the recent prevalence of tobacco use; and data from 140 countries that had done two or more surveys between Jan 1, 1999, and Dec 31, 2018, to assess the trends in the prevalence of tobacco use.
530 234 adolescents were included from the 143 countries that had done at least one survey between 2010 and 2018. 1?192?312 adolescents were included from the 140 countries that had done two or more surveys between 1999 and 2018. The most recent global prevalence of cigarette smoking was 11?3% (95% CI 10?3-12?3) in boys and 6?1% (5?6-6?6) in girls, based on cigarette smoking on at least 1 day during the past 30 days, 6?0% (5?5-6?6) and 2?6% (2?4-2?9) based on smoking on at least 3 days, and 4?2% (3?8-4?6) and 1?6% (1?4-1?8) based on smoking on at least 6 days.